The long term goals of the proposed research are to obtain a better understanding of the role of neurotrophic molecules in the regulation of motoneuron survival during normal development and in disease. A primary focus of the planned studies is the further characterization of a putative muscle-derived neurotrophic factor (MNF) that acts both in vivo and in vitro to rescue spinal motoneurons in the chick embryo from normal cell death. A related secondary goal is to begin studies to address the role of specific genes and gene products in the cell death process. A number of parameters of motoneuron development will be examined to determine whether MNF affects other aspects models of human motor neuron disease will be examined in our in vivo model in an against MNF will be used to treat chick embryo motoneurons in vivo and in vitro. Radiolabeled MNF will be used to determine whether MNF is retrogradely transported will be studied using biochemical and molecular methods for identifying, isolating and characterizing cell death genes and their products. Understanding the role of neurotrophic factors and cell death genes in normal development will aid in elucidating the pathogenesis of human motor neuron disease such as infantile spinal muscular atrophy and ALS.